Therapies for exacerbation of myasthenia gravis. The mechanism of action of intravenous high-dose immunoglobulin G.
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Biomedical subjects
Publications and source records attributed to G Aimo.
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We have investigated which of the cytokines that are relevant in the in vitro growth of multiple myeloma (MM) malignant plasma cells are actually produced in vivo by MM patients. To this end, we have measured the levels of IL-1 beta, IL-3, IL-4, IL-6, IL-7, IL-8 and tumour necrosis factor-alpha (TNF-alpha) both in sera and in the supernatant of bone marrow (BM) stromal cell cultures from patients with MM and monoclonal gammopathy of undetermined significance (MGUS). The significance of our findings is three-fold. First, IL-6 and IL-8 are produced by MM BM stromal cells, while IL-1 beta, TNF-alpha, IL-4 and IL-7 are not. Second, IL-3 is the only cytokine consistently raised in serum samples: we have also detected low levels of serum IL-6 in a minority of cases, usually in advanced stage of the disease. Third, MM BM stromal cells are active IL-6 and IL-8 producers, while both normal and MGUS BM stromal cells are low producers, thus suggesting that in the BM of MM a number of environmental cells, that would normally be quiescent, are instead activated and that, in MM, activated BM stromal cells play an active role in supporting the progressive expansion of the B cell clone.
Serum levels of soluble interleukin-2 receptors (IL2R) and of beta 2-microglobulin (beta 2M) were studied with the immunoenzymatic technique in 38 patients with primary glomerulonephritis (GN), in 10 patients with essential hypertension (EH) and in 30 healthy subjects. IL2R correlated with beta 2M (p < 0.05). IL2R and beta 2M were higher in patients with GN (p < 0.003, p < 0.001, respectively) and in patients with EH (p < 0.003, p < 0.01, respectively) than in healthy subjects. IL2R and beta 2M correlated with serum creatinine, but not with proteinuria. Our data would suggest the existence of lymphocyte activation in patients with GN. Only speculations can be advanced with regard to the observed increase in these parameters in EH patients.
Biocompatibility in hemodialysis is now regarded as a multifactorial problem and dialysate represents a main risk. Pyrogenic fractions mostly coming from gram-negative bacteria easily pass through dialysis membrane, either by backdiffusion or by backfiltration, and induce blood cell activation. To demonstrate the long-term efficiency of a 2 m2 polyamide ultrafilter in producing a pyrogen free solution, we used an experimental circuit ultrafiltering for 240 hours (500 ml/min) a bicarbonate dialysate contaminated (5 to 48 EU/ml) by a Pseudomonas aeruginosa filtrate. The efficiency was monitored by LAL-test and IL-1 PBMC so to detect not only lipid A containing endotoxins but also other cytokines inducing bacterial fractions. At the post-ultrafilter sampling port the LAL-test was < 0.005 to 0.034 EU/ml; IL-1 PBMC was below the detection limit (20 pg/ml) being 27 to 63 pg/ml at the pre-ultrafilter level. Polyamide ultrafiltration represents an efficient system to obtain an endotoxin-free dialysate and a single filter works up to 240 hours.
Although the aetiopathogenetic role of Helicobacter Pylori (HP) in duodenal ulcer and in chronic gastritis seems now well defined, we have not yet standardized therapeutic schedules to achieve disappearance of HP. This study was aimed at evaluating the efficacy of two different therapeutic schedules, colloidal bismuth alone [CB(1200 mg/day)], vs. association with amoxicillin [CB+A(3 g/day)] for six weeks, to clear HP from antral specimens in a cohort of dyspeptic patients. 49 consecutive patients (23 females, 26 males, mean age 47 years, range 22-69) with HP in gastric specimens, 30 suffering from chronic antral gastritis (CG) and 19 affected by duodenal ulcer (DU) were treated with CB (37 pts) or with CB+A (12 pts). DU patients were given also H2-blockers. These latter patients were all healed at the endoscopic control performed after therapy. 4 out of 13 DU patients (31%) treated with CB were found HP free. In 4 out of 6 DU patients (66%) treated with CB+A, HP was no more detectable. As for CG patients, 12 out of 24 (50%) were free from HP at control when treated with CB, while only 2 out of 6 (33%) when CB+A was administered. This study suggests that colloidal bismuth is more effective when administered associated with amoxicillin, but this concerns only DU patients. No relation between endoscopic healing of UD and HP presence was found.
Tumor necrosis factor (TNF) was detected, before and after dialysis, in sera from 69 patients and, at various times during dialysis, in 28 patients carefully selected for the absence of intercurrent illness. Blood samples were also sequentially collected for separation of monocytes, and cells were sonicated to detect intracellular TNF. Compared with serum levels obtained from 41 healthy subjects, basal TNF values of the unselected group of 69 patients were significantly higher (p < 0.01), independent of the dialyzer membrane. A significant increase in TNF levels by the end of dialysis was found only with Cuprophan (p < 0.01). In the selected group of 28 patients, no significant changes in TNF values were observed in sequential samples. However, a significant increase of intramonocyte TNF levels was found in Cuprophan patients (p < 0.025). Soluble interleukin-2 receptor (IL-2R) levels, measured in parallel in sera from unselected and selected patients, were found to be very much higher than healthy controls without significant changes during the dialysis procedure. While the diverse profiles of TNF obtained from differently selected patients suggest that mechanisms other than membrane biocompatibility play a role in the appearance of these low cytokine levels, the possible nature of uremic toxin for soluble IL-2R can be envisaged by detection in dialysis patients.
IgG and IgA immune complexes, mononuclear phagocytic system function, interleukin-2 (IL-2) production by peripheral blood lymphocytes (PBL), serum-soluble IL-2 receptors, tumor necrosis factor, beta 2-microglobulin and IL-1 beta, HLA-DNA polymorphisms, immuno-isoelectrofocusing, phenotype of PBL, lymphocyte cytotoxicity, activation of lymphokine-activated killer cells and natural killer cell activity were evaluated in 8 patients with tubular/fibrillary glomerulonephritis (GN). No common serologic, immunologic or immunogenetic features suggestive of plasma cell dyscrasias were found. No elements to state whether these GNs represent a new entity or just atypical forms of known GN were found.
Tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1 beta) are cytokines primarily produced by monocytes/macrophages when stimulated by endotoxin, complement-derived anaphylatoxins and the specific antigen. In the present study, the plasma levels of TNF-alpha and IL-1 beta were evaluated before and after hemodialysis with cuprophane membrane (in 9 patients) and hemodiafiltration (in 9 patients) using three high-permeability membranes such as polymethylmethacrylate, polyacrylonitrile (AN-69) and polysulfone. In vitro spontaneous production of TNF-alpha and IL-1 beta was evaluated in the supernatants from short-term cultured monocytes obtained before and after treatment. The predialytic levels of TNF-alpha and IL-1 beta were significantly higher (p less than 0.05) in the uremic population than in 21 healthy subjects taken as controls. The analysis of the uremic population regarding the mode of therapy indicated that in hemodialysis the predialytic plasma levels of TNF-alpha and IL-1 beta did not significantly differ from those of healthy subjects. In contrast, in hemodiafiltration with polymethylmethacrylate and AN-69, but not with polysulfone, the predialytic plasma levels of both cytokines were significantly (p less than 0.05) increased. No significant variation in plasma levels of both cytokines was observed after hemodialysis with cuprophane membranes. Hemodiafiltration with polymethylmethacrylate and AN-69, but not with polysulfone, brought about a consistent reduction in plasma levels of both cytokines. Detectable amounts of TNF-alpha and IL-1 beta were spontaneously produced by peripheral-blood monocytes 6 h after the end of hemodialysis but not of hemodiafiltration. These studies suggest a possible role of TNF-alpha and IL-1 beta in the biocompatibility of different extracorporeal treatments.
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28 cases of carcinoma of the digestive tract were studied in order to assess the value of assaying a new tumour marker (CA 19-9) on monitoring the postoperative course of neoplasia. CEA, a tumour antigen of more certain dependability was assayed at the same time. In the case series examined it was found useful to monitor both antigens since although CA 19-9 is less sensitive then CEA in cancers of the large intestine, it is more sensitive in carcinomas of the stomach and pancreas. These early data will have to be confirmed on larger samples but in general terms they do indicate the value of the combined monitoring of this new antigen and CEA in the follow-up of patients given surgery for carcinoma of the digestive tract.
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After a short review on the actual knowledge about the relationship between P50 of human blood in normal adults and newborns and their relative amount of Hb-CO, the Authors analyze a wide series of subjects in Whom the survey has been performed at the physiological saturations of Hb-CO. The results show that, a part from an usually high percentage of Hb-CO of still unknown origin in the newborn, the P50 of normal adults and newborns appear to be relatively stable and not shifted towards the right in spite of the progressive increasing of hypoxia induced by still physiological levels of Hb-CO.
In a wide survey on normal non-selected healthy adults, the Authors have found normal pHs in venous blood, a P50 slightly shifted to the left, in comparison with the mean values reported in other series for males and females, normal Hb amounts, normal 2,3-DPG levels, normal met-hemoglobin values and increased rates of Hb-CO. All these data and the possible relationship among them are discussed, with particular reference towards P50 and Hb-CO, which appears to be mainly raised, even if not only, in smokers people. At this regard the Authors hypothetize that if the four hemes of hemoglobin are fully saturated with CO, a right shifted oxy-hemoglobin dissociation curve of variable extent will be observed, whereas, if the hemes are not fully saturated, the curve could be shifted, more or less, towards the left. These two conditions could be coexisting in an unstable, non-enzymatic equilibrium, which could modify by itself the usual sigmoid shape (and the P50 values) of the whole blood oxygen affinity.
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AIMS AND BACKGROUND: The free/total (F/T) prostate-specific antigen (PSA) ratio is probably the most promising tool proposed to increase the specificity of PSA in the diagnosis of prostate cancer. The aim of the present study was to evaluate the clinical value of the F/T ratio in 138 patients with benign hyperplasia, 101 with untreated prostate cancer, and 176 apparently healthy men. METHODS: We used a new immunometric assay of free PSA (FPSA-RIACT, CIS Diagnostici, Italy) which has shown good analytical performance; sample handling and storage under routine conditions did not affect the antigen stability. RESULTS: The diagnostic efficiency of the F/T ratio was significantly better than that of total PSA. In patients with total PSA ranging from 4 to 10 ng/ml, at a specificity level of 95% total PSA showed a sensitivity of 7%, whereas the sensitivity of F/T increased to 70%. Using the F/T ratio as a decision tool in association with total PSA and considering all cases candidate to biopsy (total PSA greater than 3.79 ng/ml corresponding to the 95% level), we demonstrated a 35% reduction of total biopsies that would have been required on the basis of total PSA alone. CONCLUSIONS: The determination of the percentage of F/T serum PSA significantly improves the specificity of the marker, particularly in the 4-10 ng/ml dose range where unnecessary prostate biopsies can be reduced.
The usefulness of intraoperative parathyroid hormone (PTH) monitoring has been extensively documented in primary hyperparathyroidism (HPT), whereas few data have been published on its use in reoperations or in secondary and tertiary HPT. We report our initial experience with a rapid (12 min response) PTH immunochemiluminometric assay performed in the operating room during surgery in 12 patients with primary HPT, 16 end-stage renal disease patients with secondary HPT and five kidney transplanted subjects with tertiary HPT. Blood samples were taken at baseline, within 10 min after resection and subsequently at various intervals whenever needed. The mean PTH levels before and after parathyroidectomy were 230.5 pg/mL (range 69-842) and 47.3 pg/mL (range 5-184), respectively, in primary HPT, 855.0 pg/mL (416-1655) and 202.2 pg/mL (53-440) in secondary HPT, and 205.6 pg/mL (116-301) and 45.4 pg/mL (18-97) in tertiary HPT. All patients but one had a significant percentage decline from pre-excision values (mean 76.9%, 76.0%, and 76.1% in primary, secondary and tertiary HPT, respectively). While a reduction of more than 50% was observed in 30 out of 33 patients after the first intraoperative sampling, additional measurements were performed in 10 cases. On-site PTH monitoring with this user-friendly and reliable system has proved helpful in targeting PTH tests to give the surgeon a rapid and accurate assessment of the intervention. The development of optimal PTH sequence strategies with decision-focused analytical and clinical limits will improve the efficacy of "point-of-care" PTH assay and resource utilization.
Prostate-specific antigen (PSA) is a tissue-specific glycoprotein identified by Wang in 1979. It is synthesized in the prostate independently of prostatic acid phosphatase (PAP). A total of 199 subjects were divided into four groups: controls aged less than 50 years, controls aged more than 50 years, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. PSA cut-off value was set at 10 ng/ml (mean for the BPH group plus 2 SD). With this cut-off value PSA could not be used as an early predictor of prostatic carcinoma. The association of PSA and PAP in prostatic cancer increases the number of patients with positive biological markers.